This invention relates to quinazoline derivatives showing slow and continuous blood pressure reducing action and an antihypertensive agent containing the same.
An example of a quinazoline type compound employed for a known antihypertensive agent is the following compound [A] which is described in U.S. Pat. No. 3,511,836 and is commercially available as xe2x80x9cPrazosin hydrochloridexe2x80x9d: 
Also known is the following compound [B] of the quinazoline type antihypertensive agent which is also commercially available as xe2x80x9cTerazosin hydrochloridexe2x80x9d: 
The known antihypertensive agents of the quinazoline type such as the xe2x80x9cPrazosin hydrochloridexe2x80x9d and xe2x80x9cTerazosin hydrochloridexe2x80x9d are short in their half-life in blood and show their blood pressure reducing action rapidly. Therefore, these known antihypertensive agents frequently show side-effects named xe2x80x9cfirst dose phenomenonxe2x80x9d, such as orthostatic hypotension, palpitation, and tachycardia, immediately after their administration. For the reason, they have not been generally employed for treatment of hypertension at the initial stage. Recently, doxazosin mesilate which belongs to the quinazoline derivative and which shows long half-life in blood and slow blood pressure reducing action as compared with the prazosin hydrochloride has been developed. The doxazosin mesilate is reported to control blood pressure for a long time such as 24 hours by its administration once a day and seldom gives side effects such as orthostatic hypotension (J. Clin. Pharm. Ther., 14:283 (1989)).
Also known is an antihypertensive agent of a dihydropyridine type calcium antagonist. In Medical Journal (in Japanese language), vol. 30, No. 1, 101-106 (1994), this antihypertensive agent is reported to show side effects such as blush and headache after administration. These side effects arise from rapidly occurring vasolidative accessory symptoms. Therefore, the Journal indicates usefulness of Amulodipine which shows slow and continuous blood pressure reducing action. The use of the antihypertensive agent showing slow and continuous blood pressure reducing action enables administration of once a day and is effective to obviate side effects such as orthostatic hypotension and vasodilative accessory symptoms which occurs immediately after administration.
German Patent 2,457,911 describes a quinazoline derivative of the following formula [C]: 
In the above patent, there is a description to the effect that the quinazoline derivative described therein shows a blood pressure reducing action, but no pharmacological data are given.
Japanese Patent Provisional Publication 59-172478 describes a quinazoline derivative of the following formula [D]: 
The quinazoline derivative described in the above Provisional Publication is an intermediate compound obtained in reactions and no pharmacological data are given.
Under the circumstances described above, it is considered that a new quinazoline derivative showing slow and continuous blood pressure reducing action is favorably employable as an antihypertensive agent having reduced side effects such as vasodilative accessory symptoms such as blush and headache and orthostatic hypotension.
The present invention has an object to provide a new quinazoline derivative which shows slow and continuous blood pressure reducing action.
The present invention provides a quinazoline derivative having the following formula [I] and its pharmaceutically acceptable salt: 
In the above formula [I], each of R1 and R2 independently represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or R1 and R2 are combined to form an ethylene group (xe2x80x94(CH2)2xe2x80x94); each of R3 and R4 independently represents an alkyl group having 1 to 6 carbon atoms; R5 represents a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; each of R6 and R7 independently represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; and n is 2 or 3.